Augmented stress-responsive characteristics of cell lines in narrow confinements

Abstract

Adaptabilities of mammalian cells in physiological confinements of the vasculature and tissue-matrices remain unaddressed. As the adaptation to coupled chemo-mechanical stimuli becomes a pivotal factor for cell survival, we investigate here the prospect of confinement induced alterations in the stress adaptive behavior of mammalian cell lines. To comprehend the physical dynamics of cells during stress adaptation, we employ a microfluidic platform coupled with a microfabrication compatible traction force microscopy system and lipid raft imaging method to examine the confinement effect. With the variations of the microchannel height and the flow shear stress, we detect a sigmoidal shaped declination in the cellular response time. This occurs when the channel height is decreased below a threshold value of 70 μm and concurrently, stress is elevated beyond 10 dynes cm₋₂. Origin of this transition is probed to be connected to the augmentation of secreted growth factor concentration and amplification of fluid shear stress in the microfluidic environment. Two phenomena together, then, lead to elevated activation level of Epidermal Growth Factor Receptors. Thus, our findings reveal a hitherto unknown enhanced stress adaptive response of cells, which may be further exploited in the understanding of tumor progression in vivo and designing microfluidics based drug screening platforms.